Article

European Journal of Human Genetics (2009) 17, 1070–1075; doi:10.1038/ejhg.2009.5; published online 18 February 2009

Predicting human height by Victorian and genomic methods

Yurii S Aulchenko1,2,7, Maksim V Struchalin1,3,7, Nadezhda M Belonogova2,4, Tatiana I Axenovich2, Michael N Weedon5, Albert Hofman1, Andre G Uitterlinden6, Manfred Kayser3, Ben A Oostra1, Cornelia M van Duijn1, A Cecile J W Janssens1 and Pavel M Borodin2,4

  1. 1Department of Epidemiology and Biostatistics and Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
  2. 2Laboratory of Recombination and Segregation Analysis, Institute of Cytology and Genetics SD RAS, Novosibirsk, Russia
  3. 3Department of Forensic Molecular Biology, Erasmus MC, Rotterdam, The Netherlands
  4. 4Department of Cytology and Genetics, Novosibirsk State University, Novosibirsk, Russia
  5. 5Department of Genetics of Complex Traits and Diabetes Genetics, Peninsula College of Medicine and Dentistry, Exeter, UK
  6. 6Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Correspondence: Dr YS Aulchenko, Department of Epidemiology and Biostatistics, Erasmus MC Rotterdam, Postbus 2040, Rotterdam, 3000 CA, The Netherlands. Tel: +31 10 704 3362; Fax: +31 10 704 4657; E-mail: i.aoultchenko@erasmusmc.nl

7These authors contributed equally to the work.

Received 29 July 2008; Revised 17 November 2008; Accepted 8 January 2009; Published online 18 February 2009.

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Abstract

In the Victorian era, Sir Francis Galton showed that ‘when dealing with the transmission of stature from parents to children, the average height of the two parents, … is all we need care to know about them’ (1886). One hundred and twenty-two years after Galton's work was published, 54 loci showing strong statistical evidence for association to human height were described, providing us with potential genomic means of human height prediction. In a population-based study of 5748 people, we find that a 54-loci genomic profile explained 4–6% of the sex- and age-adjusted height variance, and had limited ability to discriminate tall/short people, as characterized by the area under the receiver-operating characteristic curve (AUC). In a family-based study of 550 people, with both parents having height measurements, we find that the Galtonian mid-parental prediction method explained 40% of the sex- and age-adjusted height variance, and showed high discriminative accuracy. We have also explored how much variance a genomic profile should explain to reach certain AUC values. For highly heritable traits such as height, we conclude that in applications in which parental phenotypic information is available (eg, medicine), the Victorian Galton's method will long stay unsurpassed, in terms of both discriminative accuracy and costs. For less heritable traits, and in situations in which parental information is not available (eg, forensics), genomic methods may provide an alternative, given that the variants determining an essential proportion of the trait's variation can be identified.

Keywords:

height, heritability, prediction, genomic profiling, discriminative accuracy, area under the receiver-operating characteristic curve (AUC)

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